Plasma proteins, especially albumin, account for much of the normal anion gap. The relationship between globulins and the anion gap has not received much attention except for reports of a narrowing of the gap associated with certain monoclonal immunoglobulin G gammopathies. The author presents a patient with polyclonal gammopathy, the magnitude of which correlated strongly and positively with the anion gap, along with data from 400 patients attending a renal hypertension clinic, which show a significant positive correlation between the anion gap and total globulins. These results indicate that both albumin and globulin concentrations should be taken into account when attempting to explain abnormalities or changes in the magnitude of the gap.